INTRODUCTION ‘Tuberculosis continues to be a. global health problem and even a leading killerdis- ‘ease, in:spite of great advances in medicine, particularly in the approach and strategies for initial diagnosis and treatment of this infection. In developed countries, there was, a decline in the incidence of tuberculosis (TB) for the past. two to three decades so that TB was considered a disease of the past. How- ever, since 1983 a“resurgence” has been ob- seryed, mainly attributed to the inerease in population; to association of TB with the hu- man immune deficiency virus infection (HIV); and to increased migration from high to low risk countriés. Additional factors are complacency with a. decline of progressive implementation of control measures, “in- creased poverty; and to some extent also to increased life span. It is claimed that about three (3) million individuals, die yearly of TBand there are 1.9 billion infected. with TB globally most of them will be asymptomatic. In’ 1993 WHO deelared TB to be a globitl emergency and in 1995 this organization estimated that of all children under 15 years of age, at least 180 million were infected with TB. In the Western Pacific Region (WPR) which is composed of 36 member States, 97% 6f reported cases come from five countries: China, the Philippines, and the Republic of Korea, Vietnam and Japan (1992). Regret- tably, the Philippines gave the highest mor. tality rate in 1994. DEFINITION ‘Tuberculosis is a highly contagious dis- ease caused by Mycobacterium tuberculosis TUBERCULOSIS (MTB), usually acquired by inhaling tubercle bacilli into the lungs. It is often disseminated through the body by lymphatic channels and the blood stream which may lead to digease in’ many organs such as the lymphnodes, meninges, kidney. and bones, in, fact any- where in the body. EPIDEMIOLOGY Children get infected mainly by exposure to adolescents and:adults with active TB. Although transmission of infection by child- ren is rare, they are a source/reservoir of future TB. In 1983 tuberculin skin test which detects TB infection in asymptomatic un- vaccinated children showed that in ages 1-4 years 7%, in 5-9 years 16%, while in. the 10- 14 years old 42%, are already infected. As an airborne infection; other factors that heavily contribute to the high incidence and mortality rate are poverty,,overcrowd- ing, host related factors such.as.age, poor nutrition and’viral infections. In the Philip= pines, poor access’ of our people’ to’health care has hindered greatly the diagnosis and treatment of TB thus continually increasing the pool of infected patients or the prevalence of TB. According to a National Prevalence Sur- yey in the Philippines in 1997 by Tupasi et al, 16 million Filipinos were infected with ‘Tuberculosis while, 600,000 TB. cases were actively spreading the disease. ETIOLOGY ‘The causative agent is! Mycobacterium tuberculosis. (MT)..The tubercle. bacillus grows slowly, reproduces itself every'24 to 48 hours under optimal conditions and isé dormant state for a long period of ; results ina chronic disease, fre- ‘quently with periods of apparent good health - gndoa tendency: to reactivate many years "after the initial infection. “oI the past two decades three types of MTP were known and designated as human, ‘avian and bovine. Now Avian and other forms ~ o-MT are included and classified as non- tuberculous mycobacteria (NTM). Clinically, however, NTM infections resemble and can ‘manifest: MT-like: disease in the lungs and lymph nodes. It is difficult to distinguish infections caused by tuberculosis, MT, NTM and-multidrng resistant (MDR) organisms. 7 PATHOPHYSIOLOGY ‘TTB is'an airborne infection, so that the ‘SLA! route of entry is the respiratory tract. ‘The primary infection is generally situated in the lungs; rarely it can also lodge in extra pulmonary organs like the skin, kidney, bones, GI tract or for that matter many other organs of the body. Inhaled tubercle’ Bacilli upon reaching the pulmonary alveoli for the first time, incite a nonspecific inflammatory reaction, a localized area of pneumonia with a.ten- dency to undergo cascation neerosis. This primary focus, also known as Ghon's tuber- cle, is the initial tissue response to the first infection with tubercle bacilli. No endotoxins or exotoxins have been discovered from the tubercle bacillus. Consequently, when human beings are infected, there is no immediate host response, This characteristic allows the organism to grow. more or less unimpeded until the development of an immune reaction. _. Mechanism of protective immunity at time remains rudimentary. The mani- tion of tuberculous infection in humans | an immunologic spectrum in which the ical manifestations reflect the immune tuberculin test at this time becomes \d indicates an individual is Tack of immunity initially, would \egative tuberculin’ skin test and positive later after the indi- | been treated and is recovering. ary and progressive primary tuber- 16, TUBERCULOSIS 601 culosis are principally a lymphatic diséase, Infection spreads along the chain of lym phatic glands with a definite tendency to caseate, pr and resist treatment, ‘The tendency to heal is more: marked int the pulmonary than in the nodal component of the primary complex. The initial foous may dissolve and disappear or if central easeation develops, may resolve spontaneously or become encapsulated: The lesion may finally become hyalinized and ealeified, ‘The bacilli are transmitted through the lymphatic channels to the regional lymph nodes. Caseation is part of the sequence of events. The primary focus with the aceom- panying lymphangitis and regional (hilar) lymphadenopathy is known collectively as the primary complex. ‘The primary focts is either single or multiple and is frequently subpleural in location. Instead of the wsual-benigh course, the pulmonary primary focus may undergo ex- tensive caseation.:The easeous core liquefies emptying its’ contents into'a bronchus arid leaving a cavity behind, Caseous miattér thus spills and is aspirated into other parts of the lung resulting in new’ aréas 6f broncho- pneumonia, Gravity favors spillage to depen dent portions of the hung: ‘Tubercle bacilli may indireetly gain access into the blood stream’ yia the lymphatic circulation’ which ultimately empties into the subclavian Vein through the thoracie duct; or a lymph gland may caseate into an adjacent blood vessel thus directly invading the vascular system. ‘The organs with the greatest affinity for filtering bacilli are the liver, spleen, kidneys and meninges. The myocardium, pancreas, thyroid and stomach are rarely involved. The bacilli may repeatedly enter the circulation in small numbers over a period of weeks or months; they may lodge'in various systems! and remain. quiescent without; producing disease. If seeding is massive, the lympho- hematogenous spread leads to: miliary or generalized tuberculosis. Adverse conditions like malnutrition, debility due to other dis~ eases favor spread and disease reactivation.” «Enlarged peribronchial and hilar lymph’ glands may eneroach and exert pressure ‘on’ adjoining bronchi resulting in narrowing of$02 PEDIATRICS AND CHILD HEALTH the bronchi, atelectasis and ultimately bron: chiectasis, According to M. P. Tavera among Filipino children, 89% of bronchiectasis have a tuberculous etiology A tuberculous lymph gland may. also erode through the bronchial wall forming a fistulous tract connecting the node and bronchus through which caseous material is spilled and aspirated to near and dependent areas of the lung. Infection of the bronchial mucosa results in endobronchitis. Swelling of the mucosa and/or formation of exuberant granulation tissue over the fistulous opening may cause intraluminal obstruction. If large enough, lymph nodes may compress adjacent, structure, such as the trachea, esophagus and blood vessels, Reactivation may occur after the primary or progressive primary infection has. re- mained quiescent for sometime. Reactivation of an existing endogenous focus of disease is the tertiary stage also known as chronic pul monary stage or chronic pulmonary tuber- eulosis. It is not a new infection in the sense that the individual has been reinfected by an exogenous source of bacilli. Reactivation occurs with greater fre- quency in ill-nourished individuals working under stress and strain, often debilitated by intercurrent infections. Poverty is an impor- tant factor that contributes to the rapid downhill course of tuberculosis. Chronie pulmonary tuberculosis is char- acterized by an accelerated inflammatory re- action. The bacilli create local areas of ul- ceration without involving. the regional lymph nodes. The presence of immunity ac quired from a previous infection is respon- sible for the localization of the infection and its inability to spread through the lym- phatics, PRIMARY TUBERCULOUS INFECTION AND DISEASE From the time the tubercle bacillus en- ters the body, it initiates a delayed type of sensitivity and develops the primary complex wherever it lodges, usually in the lungs. This is termed primary infection with. mycobac- terium tuberculosis (MT). The time. interval between the initial infection and the onset of disease may be fro veral weeks ig 15.2 y years, Pig, 18, L a The m of primary infection are detern immune response of mycobacterial infeetio In a majority: of cases, tuberculous infection ‘runs: a benign asymptomatic course which refleets the ime mune response of the host. It-éliminates most of the bacilli although a smail number are distributed throughout the body during the bacillemic phase. It remains “silent” and sometimes may be recognized clinically bya positive tuberculin test or hilar adenopathy and focal infiltrates on chest x-ray. The primary complex undergoes) progressive healing for life. In a minority of ea show clinical manifestation of progressive ill- ness wherever the bacilli lodge, pulmonary or extra pulmonary. This response reflects the active immune response that. fails to,eli- minate the bacilli Primary tuberculous infection may be seen at all ages especially in children before 5 years old. The age at. which infection occurs helps predict the subsequent course. The 8, the child would Fig. 15.1 A. Pulmonary focus; B. lymphangitis: ¢. enlarged hilar and mediastinal nodes; and D. localized plourisy.Fig. 15.2 Components ofa primary tuberculous complex. 1 middle: lobe; 2...regional lymphagti pleurisy between the middle and lower lobes. younger the child, the greater the severity of the local complications and the risk of Progression’ or dissemination. This is how primary” infection becomes tuberculosis disease and no longer infection In adults, there is usually a clear dis- tinetion between infection and disease. In young children in whom tuberculosis may develop as an immediate complication of the initial infection, the two stages are often less distinct. CRITERIA FOR THE DIAGNOSIS OF TUBERCULOSIS In children, the diagnosis of tuberculosis iS usually difficult. A high degree of aware. fess and suspicion is a prerequisite. Symp. toms in children are not typical. There are No pathognomonic x-ray findings. Sputum ie. obtained and is often negative even n culture DIAGNOSTIC CRITERIA ~»L. Exposure to TB sputum positive adults > usually in the household. TL, Mantoux test 15. TUBERCULOSIS 503 A primary pulmonary foous in the tight ‘and lymphadenitis; 3. peritracheal lymph nodes; and 4. localized * PPD supply distribution scheme and re-supply points * Correct application and accurate reading TI. Signs and symptoms any 2 or more IV. Chest x-ray; consider * Availability + Problems Clinical Signs and Symptoms (Any one or two or moré are considered positive) — cough with or without wheezing for more'than 2 weeks — unexplained fever for more than 2 weeks ~ failure to gain weight, weight loss ~ unexplained poor appetite — painless cervieal lymphadenopathy — failure to respond to.2.weeks appro- priate antibiotic therapy: for lower respiratory tract infection. Classification. A classification was pro- posed by the National Consensus on Child- hood Tuberculosis: in 1997 based on the American Thoracic Society and the Centers for Disease Control with the 3 stages of tuberculosis: exposure, infection and disease, e the clinician in the evaluation and treatment of the patient.804 PEDIATRICS AND ONILD HEALTH Qlass I "TB Exposure Class 1 "TB Infection Class TIT TB Disease Class IV ‘TB Inactive I, TB Exposure. A child who has been exposed to an adult/adolescent with active disease, negative mantoux tuberculin test, has no signs and symptoms of TB and nega tive chest radiograph. The incubation period from the time of infection to the development of a positive tuberculin reaction is 2-10 weeks. Delayed hypersensitivity to tuberculin may develop up to3 months after infection and before the clinical signs and symptoms develop or the chest x-ray becomes positive. Severe TB especially meningeal and dis- seminated disease can develop in less than 3 months in children less than 5 years of age. Therefore, young children. in the. ex. posure stage should receive treatment until infection can be excluded with a repeat fubereulin test 3 months after contact with active TB has been done. UL. TB Infection (preclinical stage). A child With or ‘without history of exposure to an adult/adolescent with active TB disease, has positive maritoux test, has fio signs and symptoms of TB and negative chest radio: graph is said to have TB infection. The risk of developing TB disease is bet- ween 5-15% during the first 10 years after primary infection, with the highest risk developing in up to 50% of infants within 3. 9 months of infection, 25% in children 1-5 years of age within 1-2 years and 15% in adolescents, The risk of TB: disease, which may be severe,and, progressive depends on several factors such. as age,. nutritional status, bacteriological status of adult source and intensity, of contact Ill, TB Disease. A child who has active ‘TBhas 3 or more of the following criteria: 1. exposure tovan adult/adolescent with active TB disease 2, positive Mantoux tuberculin test 3, signs and symptoms suggestive of TB 4. abnotmal chest radiograph suggestive of TB 5. laboratory findings suggestive of TB © histological; ‘cytological, biochemical, immunological and molecular) Although each child with ‘TB should be ‘ individualized, the consensus aan 1 that a child with 'B should have at 7 cut of the 6 erteria to satlefy & Alagoas TB disease, In contrast to early TB, symptoms are a ty very helpful in the diagnosis of extrapul. a monary or progressive TB, In addition to Ps the more common and general symptoms of the fever, anorexia and loss of weight, delayed - menarche in girls, signs or symptoms ma referable to other organ systems may persist. ng In the presence of any of the following, the bi patients should be referred to a hospital for * evaluation and treatment: rec sinus in the neck; mL large painless lymph nodes in the neck, ind axilla or groin; The angle deformity of the spine; ree joint or bone swelling or sinusé3; TU ‘unexplained abdominal mass or ascitis; a change in temperament, fits’ or ‘con = vulsion vae IV. TB Inactive. A child/adolescent Tas with or without a history. of previous,TB, mi with or without provious chemotherapy, has Pre radiographic evidence of healed/caleified TB, pini positive Mantoux test, no signs and: symp- toms suggestive of TB and negative smear/ tivi culture for tuberculosis. Res TUBERCULIN SKIN TESTS. 1 Multipuncture Test. “In the Philip- pines where BCG coverage in the population is high, the use of multi-puncture test must be highly discouraged because they may actually provide conflicting information that causes more confusion than clarity. (Dr Jeffrey Starke, PPS Convention 1997). ‘The Mantoux Tuberculin Test. The Mantoux test is the gold standard and the only way to diagnose TB infection. However, a negative Mantoux test should never out TB in a child. ‘The tuberculin skin test is a tia demonstrating infection with M, Tubere: losis. It is based, on the fact that hae with M. Tuberculosis produces sensitivity 1 q certain antigenic components. of the orE% nisms that are contained in culture: called Tuberculin. ce15, TUBERCULOSIS 605 ‘here are 2 preparations + “ig, OT=old tuberculin Do waned sensitivity) 9 PPD = (purified Protein Derivative) ~ Recent star advanced or overwhelm- ise aaa REST ee ing infection with M. Tuberculosis 2. Factors related to tuberculin used. improper storage contamination improper dilution . adsorption chemical denatu- a tuberculin, syringe with a 1/2 inch gauge 96 needle. With the bevel up inject 0.1 mL, PPD intradermally into the volar surface of : fhe forearm, A discrete pale wheal of 6-10 a fam must be produced which will last for 10 etatrdis ee faduration is measured transversely to,the ee Tong exis of the forearm and recorded in MPRA millimeters. drawing into syringe ; WHO Recommendation. ‘the WHO ciocwond eacnen eommends the use of 2TU PPD RU23, 0.1 4. Factors related to reading the tesband fb intradermal, to be read in-72 hours, An secs tiacnialia * induration of >6 mm is considered positive. inexperienced reader The National Co: nsus on Childhood TB: conscious or unconscious bias recommends that the Mantoux Skin Test 2 error in recording TUPPD be conside: (+) if it gives a ATS, Diagnostic Standards. and Classifi- Teaction 26 mid, induration-for nonivacti: cation of Tubereulosis, Am Rev. Regs: (Dis nated infants and children, 210 mm. if BOG 1990 Vaccinated below 5 years. However theDOH Tubereulin Skin. Test Recommend- vt ask Force for Childhood TB ‘considers 28 ations: 3, mm. as positive. Gazed on the’ National 1. Children for whom immediate skin s Prevalence Study by Tupair et al., Philip- testing is indicated. 3, pines 1997 en contacts of persons with eonfirmed p Locallly;:the Mantoux fest has’a sensi of suspected infectious: tubereu- url tivity of 19-41% and specificity of 77-100%. losis: Fiietors Causing Decreased Ability to Respond to Tuberculin Test 1. Factors related to the person tested p Infections a Viral (measles, mumps, chicken st pox) ay Bacterial (typhoid fever, typhus, at leprosy, pertussis, overwhelming br, TB Tuberculous Pleurisy) Fungal (South Amerigan mouth he ‘actimo blastomycosis) ie We virus “vaceination (measles, ‘miumps, polio) metabolic derange- ments (chronic renal failure) Nutritional factors (severe protein depletion) = Diseases affecting lymphoid organs (Hodgkin's disease, lympho: ‘ehronic lymphocytic leukem: sarcoidosis) = Drugs (corticosteroids, immunosup- |, (Dresbive agents) 2 — children identified-as: contacts of family members or associates in jail or in prison in. the last5 years. — children,.with radiographic or clinical findings suggestive of TB. — Before initiation, of, immyno- suppressive therapy, Children who should be tested annu- ally for TB. Children infected with HIV. Institutionalized adolescents, Children who should: be tested. every. 2-3 years: children exposed to, the following individuals: HIV infected, homeless, instita- tionalized adolescents or, adults, drug addicts CX Children for tuberculin testing at.ages | 46 and 11-16 years, wey Children without, specific “ate factors whe reside in high valence areas, 1 aap indies§06 PEDIATRICS AND CHILD HEALTH ildren for whom immediate and p rm fe skin testing should be con! dered vi Children with medical risk factors inelu- ding diabetes mellitus, chronic renal failure, jalnutrition and congenital or acquired immunodeficiencies. (American Academy of Pediatries, Com- mittee on Infectious Diseases, Pediatries 1996) BCG and Tuberculin Skin Test. BCG increases reactivity to a subsequent tuber- ulin test. Fifty percent of newborns given BCG reacted to tuberculin at 6-12 months to 5 years. Tuberculin reactivity is unlikely to be present 10 years after vaccination if there is no TB exposure. BOG is not recommended as a diagnostic tool because of the limited number of subjects tested in studies made, the boosting effect of BCG on tuberculin test and the danger of disseminated BCG-osis in severely mal- nourished or immuno-compromised children. Chest Radiographics. Findings are non-specific, Hilar adenopathy with or with- ‘out a parenchymal focus is seen in 92% of immunocompetent hosts. Chest radiographs may be normal in up to 10% of patients who have proven primary tuberculosis. ‘The common chest x-ray finding among muno-compromised host is a diffuse reticular nodular pattern, Laboratory Diagnosis. Bacteriologic: diagnosis is difficult, beeause the child does not expectorate. In prolonged TB, < 10% of AFB stain is» positive and < 50% of AFB culture is positive. In children > 6 years of age, gastric lava. ge may be done to obtain the specimen but these maybe falsely positive due to gastric Saprophytes which are acid fast, ‘Traditional culture will take 4-6 weeks for bacterial isolation and 3-4 weeks more for susceptibility testing. Bactec Radiometric System (Rapid Culture) will take 1-2 weeks of isolation and 4-T days more for susceptibility testing. Immunoassays. Elisa (Enzyme linked Pearaecten! assay) is the most popular. joassay for antigen or antibody detec. _ tion and Elisa serologic should be readily in developing countries. ‘isa simple, workable and reproducible ‘that can process many samples at any one time and ean prodies results jy « 4-6 hours. Its sensitivity depends on the “ prevalence of TB in the area being higher in the highly prevalent, areas. Specificity wi u depend on the antigen used with value € approximating 100% for highly purified I antigens, 6 antigen or antigen 6, p Poly Chain Reaction (PCR). This ' involves the amplification of DNA or RNA, ‘The result is sufficient to diagnose TB in children. It is extremely sensitive but contamination may lead to false positive results. It is useful in the determination of drug resistance. Source: National Consensus on Childhood TB, November 1997 ‘Summarizedby Belen B. Santiago, MD. Center for TB in Children. PROGRESSIVE PRIMARY TUBERCULOSIS After an incubation period of 2 to 10 weeks, necrosis of the primary focus may. develop further. It enlarges with peripheral extension, gets walled off and is ealeified or disappears; or the lesion may be progressive. Since this focus is situated in the lungs, prog- ressive pulmonary tuberculosis develops in the form of caseous pneumonia, New areas of bronchopneumonia with tendency to ease- ation is develop as a result of broncho- genie spread to other pulmonary segments of the same or opposite lung. Occasionally, t subpleural necrotic areas perforate the pleura causing pneumotherax followed by empyema. ; Clinical Manifestations, Progressive primary TB is rare but is more severe: The ‘ greatest risk of severe locally disseminated 3 lesions depends on the age of the patient, a acquired and non-specific resistance of the host as in children with poor nutrition, repeated infections, poor weight, gain or failure to gain weight, persistent fever for weeks, The child appears ill, cough becomes distressing. Intensification of the symptomatology of primary infection should arouse the cion that the infection has taken # progres sive course. The child by now appears. ill due to the daily appearance of fevera definite upward trend, Cough ly becomes di FF Abnormal physical signs are easily elici Breath sounds are increased and fine 7 Gepitant rales are audible, The greater the e Tang area involved, the more sevore the dys ipnes. Hemoptysis is rare and occurs in those with cavitary disease. {Due to the greater number of tubercle }eslli there should be no difficulty in demon. Sgirating,bacilli in. the sputum or gastric fentents by microscopy. Cultures may be Ipecessary for drug susceptibility studies, Roenigenography. There may be an trea of rarefaction, within. the. pneumonic density, The hilar and paratracheal lymph nodes are grossly enlarged. Bronchopneu- r monic foci may be seen scattered in one or both lungs favoring the dependent: areas Atelectasis is seen in those with bronchial obstruction. Bronchography may in time demonstrate bronchiectatic changes. Prognosis. With antimicrobial therapy mortality rate has. been reduced-except. in young children below 5 years of age suffering from malnutrition, where residuals of disease may be extensive and irreversible among survivors, Some may ultimately develop bronchiectasis and chronic cor pulmonare. ‘Treatment. Surgical resection should be considered if after 18 months of chemo- therapy a residual cavity persists and if {tubercle bacilli continue to be present in the sputum or gastric contents. ‘The ideal guide as to the duration of treatment is the bacteriological conversion and the radiological changes. a re fan - SoerreorSS CHRONIC PULMONARY ERCULOSIS tivation Tuberculosis, Phthisis) | Ghronic pulmonary tuberculosis is a characterized by pulmonary localiza- whereas primary infection which is also ary in location represents the initial ‘of a generalized systemic infection. but more often years is the time wn these two stages. » pulmonary tuberculosis is endo- representing reactivation lesion, This tertiary stage 15. TUBERCULOSIS 507 may be seen in Filipino children-as a8 five years of age but is more common I children over 10 years of age in girls and generally among the malnourished, The initial lesion is an area of pneumo- nia usually in the apical or infraclavieular areas with tendency to ulceration leading to cavity formation. Other areas of the lung are subsequently infected through bron- chogenic spread. Healing is either by comp- lete resolution, encapsulation by fibrosis or calcification. A small cavity may close spon- taneously through apposition of its walls or inspissation of its contents sealing off the draining bronchus at: its: bronchocavitary junction. An open healed cavity which is the result of effective drug therapy may persist The characteristics of such a cavity is that the wall is smooth, thin and devoid of peri- focal inflammation. Clinical Manifestations. As 2 rule, cases with minimal pulmonary infiltrations are asymptomatic without abnormal physical signs until such time that the disease has extended involving more lung areas. Cough is not distressing initially; the child is afebrile or may exhibit slight rises of temperature. These symptoms tend to recur. Bach episode is associated with gene- ral malaise, easy fatigability, anorexia, loss of weight, apathy, and irritability: Initially, physical signs are meager. Fine crepitant rales may be heard over the apical areas of the lungs and are best appreciated on deep breathing. ‘The symptomatology intensifies as more areas of the lung are involved. Cough be- comes distressing, fever reaches higher le- vels, tends to persist and there may be dysp- nea. Easy fatigability, sweating, anorexia and loss of weight are other symptoms. Even in advanced stages hemoptysis is unusual although it is mare common when compli- cated by bronchiectasis. Due to the large bacillary population direct examination of the sputum or gastrie contents reveals the presence of bacilli a Roentgenography. The infiltrates) in chronic pulmonary tabereolsid- wil are easily seen by roentgenogram psi re eal im location, Fock inthe.808 PEDIATRICS AND CHILD HEALTH extreme apices may not be visible in a con ventional chest film and ean only be seen in & lordotic position. A highlight within a pulmonary shadow represents a cavity. It is, not always possible to distinguish between ‘small infiltrates of primary infection and those of chronic pulmonary tuberculosis. The fone distinguishing feature is that hilar lymph ‘node involvement is present in primary infection. The age of the patient is ‘another clue as chronic pulmonary. tuber- culosis generally occurs in older children over 10 years of age. Prognosis. In children debilitated by previous or intercurrent infections and by energy/protein undernutrition, the pulmo: nary lesions tend. to be unstable and may ‘rapidly progress. Reactivation or progression can be prevented if the underlying disease is promptly and adequately treated. Treatment. The best drug regimen for both untreated and retreatment cases is INH, rifampicin, and. streptomycin, Table 15,6. Ethambutol js often added as a third drug in place of streptomycin in cases of allergy to the latter.or the child’s refusal to have injections, Ahigh protein diet with liberal amounts of fat: is recommended. Vitamins; especially ‘A.and C should be prescribed, ‘Treatment need not be instituted in the hospital. Most cases can be treated at, home. Absolute bed rest is indicated only for the acutely ill child. It may be necessary, how: fever, to limit social contact during the in- fective stage of the disease so as to minimize the danger of transmission to others, Regular bacteriological examination of eee Periodic roentgenograms ‘A9.a guide to evaluate the effectiveness of therapy, éttusion is tuberculous’ in’ étlolo majority of cases. tm the ples Pleurisy results from ari extension ofthe = disease from a subpleural focus. For thiy ta reason the effusion is located’on the samg oe side as the diseased lung, On rare oetasi be the pleura is infected via the hematogenaus route. nec Clinical Manifestations. The disease mas presents itself'in an acute manner in most emb cases. Seldom is the onset insidious, Pever prey and cough are the outstanding ‘symptoms, ress ‘The degree of dyspnea is proportional to'the and amount of effusion. Older children’ able to the verbalize may complain of chest anid back defe pains, Findings on physical examination depend on'the amount of effusion present. en ‘The tuberculin reaction is‘always ‘pro minently positive. A state of anergy is ex: ; tremely rare ‘The fluid obtained by thoracentesis’is oa clear and amber-colored. Occasionally, it is paeH slightly cloudy. Rarely it is hemorrhagic: The tea albumin content is increased proportionate cheat to the number of cells. The level'of sugar'is ae variable in children and without anydefini- tissu tive pattern; Cytology reveals a predomi fvierd nance of lymphocytes. Culture of the fluid is ¢ usually negative. beha Pleural biopsy may be of diagnostic of the importance but should not be attempted/in tional the very young and in those withiseant amount of fluid because of the danger of puncturing the lung. Roentgenography. ‘There is a diffuse haziness usually basal in location devoid of pulmonary markings blurring the outline of the diaphragm and obliterating the casto- phrenic and cardiophrenie angles. If amount of the pleural fluid is si the mediastinum and heart are displaced the opposite hemithorax. ‘ a Prognosis. The immediate and ultimat® arom: prognosis of pleurisy with effusion is bright#t in children than in adults. The'risk loping chronic pulmonary tubereu pleurisy is twice higher in children ten years of age or older at the time occurred. Empyema is rarely 8 complication of tuberculous | Ac distressing> : > , : 2 t r E ’ k 2 adhesions and fibrosis. with: conse IAbrothorax, traction: on the medias. sand its contents and compensatory Corrective surgical decortication She required to correct the structural ty whieh tends to worsen with time. Sefreatment. Thoracentesis is’ not only but life-saving in’ those with effusions causing. cardiorespiratory embarrassment. Early evacuation ‘of fluid prevents hemic spread and averts the prog. tession of the disease: process in the pleura gndunderlying lung. Steroids do not hasten the absorption of fluid -although: rapid Wefervescence is attributed to it. EMPYEMA. Empyéma-liké pleurisy is usually anila feral and’oecurs in the same side'as the dis- eased lung! The underlying pulmonary pathdlogy is generally extensive and necro: fizing. Emipyema may’ extend through the thest wall via'a pleurceutaneous communi tation” which externally resembles a soft tissue abscess, Rupture occurs due to feretsed intrapleural pressure Clinical Manifestations. Empyema behaves like pleurisy in that the intensity ofthe signs and symptoms is directly propor fional to the‘amount of fluid present. Chest nd back pains are not as prominent as in pleurisy but the child appears more critically {ll in eripyenta: The fever is high and does ot readily respond to drug treatment unless tombined with drainage procedures Roentgenography. Of diagnostic impor- tance is the presence of a fluid level, The Presence of a pyo-pneumothorax indicates Mipture’ of the lung, At times, osteomyelitie Ghanges’in one or more ribs are demonstrable. ©) Prognosis. Because the child possesses remarkable ability to resolve thick pleural ‘Muidates early surgical intervention like prtication is best delayed. If after 6 esolution has not been achieved, ‘delay is not advisable. it: Better results in terms of expansion and less pleural resi- ‘obtained with thoracotomy than needle thoracentesis. A thora- its instillation of antibiotics 15. TUBERCULOSIS 609 and periodic washing of the pleural cavity with sterile saline solution s0 as to Temove the debris which interferes with pulmonary expansion, Surgery is indicated for those with patent bronchopleural fistula and extensive pleural residues. Of prime, importance is antimicrobal therapy of wide coverage, for tubercle bacilli and for the pyogenic invaders. EXTRA PULMONARY TUBERCULOSIS ACUTE MILIARY TUBERCULOSIS Miliary tuberculosis i8 @ serious primary complication due to massive inva- sion of the blood stream by tubercle bacilli. The seedings may easily escape dete being microscopic in size. Among malnout rished children, infants and untreated eases, meningitis is'a common feature of miliary tuberculosis. For this reason, an early spinal tap should be considered., Clinical Manifestations. The onset of miliary tuberculosis may escape detection since the symptoms of anorexia, weight loss, cough and: low grade fever may be: erro- neously attributed to the underlying primary disease or to. nonspecific respiratory infec- tions. The onset may be heralded by an ab- rupt rise in temperature which has. ten- dency to persist. Miliary tuberculosis: may present itself as any of the following clinical forms: typhoidal,, pulmonary or meningeal, In. the typhoidal form abdominal mani- festations predominate, ie., abdomen is ten der, liver and spleen are enlarged and the childs appears toxie; respiratory symptoms fand sign of meningitis prevail in the meningitic form. There are-no- abnormal physical signs in the early, phase of the disease. Fine crepitant rales may be-heard in the terminal stage. Enlargement of the liver; spleen and superficial lymph nodes are present in about half of the cases of miliary tubereulosis. Retinoscopy may demonstrate the presence of chordidal tubercles. ‘The tuberculin test generally positivein the early stage of miliary tuberculosis reverts to negative as the disease progresses, omilt> ‘ous of impending death. As the disease res- ponds favorably to treatment, the{$10 PEDIATRICS AND CHILD HEALTH eaction returns'to positive. Conversion is, ‘considered-a good omen. The total white blood cell count may be hormal or may reveal slight leacocytosis with yinance of lymphocytes: ‘Tubercle bacilli are rarely demonstrated fn the sputumi or gastric contents. Blood teltire and bone marrow aspirates may yield tubercle bacilli. Roentgenography. There are no radio- logical findings in the early stage of the @isease. Some cases have normal roentgeno- grams, the diagnosis being accidentally discovered on the autopsy table. The typical findings consist of multiple, tiny, fine, dis- crete mottled densities, scattered diffusely ‘and symmetrically throughout both lung fields, The hilar and paratracheal lymph glands are enlarged. Prognosis. Antimicrobial therapy has completely altered the course of miliary tuberculosis. No child survived prior to the discovery of specific anti-TB drugs. With effective chemotherapeutic agents, most of the better nourished children survive. Metastatic foci not adequately reached by drugs can silently persist without being dlinically recognizable. These quiescent foci often reactivate at a later date. It is for this reason that children who survive miliary tuberculosis should remain under medical surveillance. ‘Treatment, Prompt and intensive mul tiple drug therapy is imperative. Treatment should be prolonged until the infection has been arrested and controlled TUBERCULOUS MENINGITIS ‘Puberculous meningitis is a frequent type of meningitis encountered in childhood as observed in developing countries. Among weak malnourished children it is almost always fatal even if treated. It is an un- eommon complication before the age of six ‘months and is more frequent during the first three years of life. Measles, pertussis, trauma and steroid therapy are linked with forms of primary infection that ce of meningitis. i's. Meningitis is always ‘toa tuberculous process elsewhere in the bodly and is generally associated with active pulmonary disease, Tubercle baci fre transported ‘via the lymph or blood stream early in the course’of untreated pri: mary infection. Bloodborne bacilli reaeh the brain where they’ may: lie dormant in the choroid plexus or in a subcortical foeus. Dis- lodgement of the bacilli into’ the subarach- noid: space. produces contamination: of the meninges: The sudden flooding of the sub- arachnoidal: space: by. massive numbers of bacilli and necrotic debris from’ a’ rapture tuberculous focus in a highly sensitized individual evoke @ violent inflammatory reaction of the meninges. Head trauma is ‘often mentioned in the clinical history as having preceded meningitis. ‘A meningo-encephalitis is the prevailing feature of meningitis. The gelatinous exudate collects around the brain stem and results in obstruction of the basal.cisterns with con: sequent hydrocephalus, Caseous tubereles tend to be more numerous atthe base of the brain than over its convex surfaces, Arteritis with consequent occlusion of the vessels, ischemia and softening of the brain occur, Involvement of the cranial nerves is the result of pressure exerted by thick exudate ‘at the base of the brain. Visual disturbances including blindness is either due to the exudate or edema around the optie nerve or to direct involvement of the optic nerve or the visual area of the cortex. Clinical Manifestations. There are three stages in meningitis that closely follow one another; namely, an early stage of irritability, the pressure or convulsive stage and the paralytic or terminal stage. ‘The onset is gradual and the prodromal symptoms easily overlooked are anorexia, apathy, irritability, headache, vomiting and slight to moderate fever. As the intracranial pressure increases, the child exhibits alter nate periods of drowsiness and irritabilit The fontanels bulge in infants and there m@ be changes in the optic dises. The pupil unequal or constricted in most cases. SH® bismus is common. Tubercle may. fundoscopy in those with coexisting miliay tuberculosis. The temperature: By then there are definite signs irritation such as nuchal igi and Br commor constip the ebil coma. 1 and thé In. the tuberer treater about t childre An sing le priman tion of with P of sym charac obstru As ly ise itehil xanth ance ¢ celluls have : chrom which at the chiefly nished as the level i spinal: hours; culous cially ¢ nearly Pr therar relapsi ski's signs). convulsions are during this period, Vomiting and are usual, In the terminal stage ‘sinks intoa deep stupor and finally ‘The pupils become dilated and fixed, picture is one of decerebrate rigidity. 7 Gnthe terminal, stages of meningitis the fabereulin reaction becomes negative, In un- eeated cases the entire course averages shout three weeks or slightly longer in older An unusual form of meningitis compri- ‘sing less than a fifth of cases are those with spinal cord infection. The obstruc- fion'of the spinal canal may be associated with Pott’s disease. In this type, the duration ofsymptoms is usually prolonged and it is characterized by spinal cord symptoms and obstruction. ‘As'a rule, the cerebrospinal fluid initial. lyis clear or slightly opalescent. Seriously iilchildren and those with spinal block have xanthochromic fluid. The physical appear- ance*of the fluid is directly related to the cellular content. Clear and colorless fluids have a lower cellular count than xantho- chromic and opalescent fluids. The cell count, which may be normal or slightly increased at the onset, rises gradually, The cells are chiefly lymphocytes. Sugar levels are dimi- ished at the onset and continue to decrease as the disease progresses. Decreasing sugar | level is considered a bad omen, When the spinal fluid is permitted to stand for several hours, a delicate pellicle usually forms. Meti- eulous examination of the fluid and espe- tially of the pellicle for tubercle bacilli will early always reveal bacilli. Prognosis. Since the advent of chemo- "therapy fewer children die of meningitis and felapses are rarer. The fate of tuberculous 1 Meningitis is dependent on the activity of the underlying tuberculous disease. The mor- F rate is extremely high in eases asso- ‘tiated with miliary tuberculosis and caseous Tits outcome is also influenced ‘age of the patient and by the child's status. Infancy and adolescence 15. TUBERCULOSIS 611 attended by marked personality changes, tment. Initial drug treatment of tuberculous meningitis co of a two- month intensive phase with isoniaaid, riffam- Picin, pyrazinamide, and streptomycin or ethambutol followed by isoniazid rifampfein + ethambutol/streptomycin daily or 3x a week DOT for ten months, The use of corticosteroids helps in preventing the oceurenee of obstruction and to.a lesser deg- ree in relieving obstruction, common. in. the later stages. Intrathecal administration of any drug should be avoided. Supportive and symptomatic treatment is. important. Orthopedic management and rehabilitation may be necessary in some children because of disturbing sequelae. TUBERCULOMAS Tuberculomas may oceur in any partof the nervous system but are more’ frequent in the cerebellum and brain stem. These are isolated foci of caseous and: proliferative tuberculosis. Tubereulomas result from blood stream invasions and-are secondary to a focus in the lungs or lymph nodes. Proximity of the tuberculoma to the meningeal surface causes a localized meningitis. Except: for signs of inereased intracranial pressure, the paucity of the spinal fluid findings in-well encapsulated tuberculomas leads toa diag- nostic Clinical Manifestations. Tubereulo- mas behave like intracranialtumors. Diagnosis is difficult and many tubercalomas are unexpectedly discovered during operation for other causes. The most important diag- nostie criteria are evidence of meningeal irri- tation, increased intracranial pressure and signs of a focal lesion in the central nervous system in a child with proven tuberculosis in the lungs or in other systems. ‘Prognosis. The course is one of slow progression. If untreated, the disease termi- nates in a generalized tuberculous meningi- tis. Death may-also occur from pulmonary ‘tubereulosis or from tuberculosis’ of other ms. vstrveatment: This consists’ of prolonged antimicrobial therapy and surgery in: very selected eases. In those where surgery isinot feasible, it may be necessary to reduce in-B12 PEDIATRICS AND CHILD HEALTH tracranial pressure by performing a shunting Since primaty infection is principally a pulmonary disease, the peribronchial and hilar glands ‘are the first set of nodes to manifest signs of infection. Through direct ‘extension, the lower cervical chain of glands may also be involved. The inguinal and axillary glands are tare sites of tuberculous infection, unless the portal of entry is through the skin. Should the bacilli enter the body by way of the digestive tract the mesentric lymph glands are correspotidingly involved. Calcified mesenteric lymph nodes can be detected by x-ray examination of the abdomen. If the primary infection is localized in the tonsils or in. the nasopharynx, the bacilli are transported to the superficial cer- vical lymph. glands. Contrary to prevailing opinion, enlarged cervical lymph nodes in Filipino children are more often. caused by infections other than tuberculosis, suchas atypical mycobacteria or as part and parcel of pyogenic infections in. the scalp and oronasopharynx. Hence, a diagnosis of tuber- eulosis is mot warranted unless supported by. @ positive tuberculin test and other teria. In some instances it may-be necessary to'resort to biopsy: Involvement of more than ‘one group of superficial nodes is a charac- teristic feature of protracted: hemaogenous tuberculosis, Clinical Manifestations. Initially, the affected nodes are painless, firm, discrete and movable. As the nodes enlarge, they become adherent to each other and anchored tothe surrounding tissues and skin (scro- fuloderma). Thereafter, the glands soften due to easeation necrosis and evcntually rupture into-the surrounding tissue. The caseous Processimay also erode the skin and drain % ‘The sinuses tend to persist. and : lly: resist: treatment. Altogether the is one of dirty, wet looking ulcers: Its in disfiguring sears. Despite of inflammation, there is nor tenderness. The lack of and pain at the site should exclude acute pyogenic infections, usually accompanied by fev eh ae ness and pain. The possibility of with atypical mycobacteria: should not ty overlooked. Because tuberculosis is a docigh disease scrofulodermas are only: seen in children of families belonging to the lower social scale. Treatment. Response to chemo! is slower in eases of lymphadenitis; INH: be given alone in the early stagesif the adenitis is not associated with: active: pul- monary disease and if there: is no local caseation. The fastest response seen even in cases of scrofuloderma are: with:drug combinations which include INH, rifampicin and streptomycin. When suppuration occurs and secondary infection develops, wider coverage with antibiotics may be necessary Surgical excision of the glands is neither necessary nor is it recommended. Indicision for drainage purposes may be done for large caseous masses. The value of enzymes and corticosteroids as adjuncts to drug therapy is of doubtful value. TUBERCULOSIS OF THE INTESTINAL TRACT AND MESENTERIC LYMPH NODES Primary tuberculosis of the intéstinal tract: is probably nonexistent in the Philip- pines because Filipinos'like’ most Asians‘aré not fresh milk drinkers unlike Caucasians: Involvement of the intestinal tract withiex+ tension to the mesenteric lymph nodes'and peritoneum represents a form of surface ex: tension as a result of ingestion of bronchial seeretions containing tubercle bacilli excerted by a caseous pulmonary focus. ‘The bacilli are taken up by the lymphoid tissues found in the Peyer's patches which eventually drain into the regional lymph nodes. Tuber culous enteritis characterized by i ulcerations may be located in any part of the gastro-intestinal tract but the lowerhalf of the jejunum, the ileum and cecum possi vertel‘enterocolitis, with tenesmus, abdomin t F ninal pain, jand tendernoas and a chronic diarrhea which at times may be bloody. Cicatrization of the jekeers can give rise to obstructive mani festations. “A Enlarged caseous and caleifi : nd calcified mesentrie Iymah glands (bos mesenterica) are often accidentally discovered in a roentgeno; vy enogram @fthe abdomen. The enlarged caseous me. gentric lymph nodes incite a local inflam matory Teaction and result in adhesions which may interfere with intestinal motility and produce mechanical ileus leading to intestinal obstruction. This may also result when 2 mass of enlarged nodes adheres to the intestine causing compression. Pressure ‘on the portal vein dilatation of the sv ay cause ascites and ial abdominal veins Chylous ascites due to pressure of enlarged lymph nodes, on the thoracic duct is one of rarer complications. Proximity of some tebral column explains the sease extension to the glands to the v possible ma vertebral bodies ner TUBERCULOUS PERITONITIS ‘The peritoneum becomes involved either through the lymphatics, resulting in a localized plastic peritonitis or through the blood stream. In the latter case the peri- toneum is studded with miliary tubercles and the peritonitis is generalized and not localized. ‘Tuberculous peritonitis with effusion may occur alone or is closely associated with polyserositis (Pick syndrome, Concato's Higease) in which case other serous-lined 4 simultaneously or suc spaces are affected cossively. Clinical Manifestations. ‘The rounded distended appearance of the abdomen suggests the diagnosis. The usual signs of fluid are present. Paracentesis yields a clear, colorless or yellowish, slightly cloudy, fluid hich is usually sterile on culture, Cell count is elevated with lymphocytes predominatine: Protein content is high and tuberele bacilli hay be cultured in some cases. In severe eases because of adhesions ind matting of 1. TUBERCULOSIS 513 irregular nontender masses, fat all necessary, exploratory paracens esis should be done carefully sinee there te tesis shou ly done caret ince tI ae Perforating the intestines should Su be adherent to the abdorninal wal Surgery provides the only means of severin nding adhesions causing obstruction. TUBERCULOSIS OF THE AND SPLEEN UES Involvement of the liver is always secon- dary to tuberculous lesions elsewhere, and is an integral part of a generalized infection. Bacilli reach the liver through the hepatic artery or from necrotizing lesions drained by the portal vein. In miliary hepatitis tuber- cles are seen all over the peritoneal surface and scattered throughout the liver sub- stance. The tubercles may coalesee and form masses of caseous granulation tissue which may open into and infect the bile duets. Portal lymph nodes can produce jaundice by sion of the neighboring bile duets, Large “solitary” tubercles can occur singly or in numbers. They may break down and cause massive caseous tuberculosis. Caseous masses may become infected secondarily and form abscesses. Liver calcifications due to tuberculosis have been demonstrated on x-ray. ‘The spleen is similarly involved as the hiver: in faet, itis seeded with tubercle bacilli to a greater degree. Of all the organs, the liver and spleen have the highest affinity for filtering tubercle bacilli. ‘TUBERCULOSIS OF THE SPINE (uberculous Spondylitis; Pott’s Disease) ‘The most common site of tuberculosis of the skeletal system is the spine, followed by ike weight-bearing joints, the hip, kes Pn eT in the order of frequency, the and ip lumbar, cervico-thoracie and limbo: tnorat vertebrae may be involved. Peak pe Saeco of spinal tuberculosis occurs duit the first five year me age. The disease within ge «che initial primary infection, Trans amvetimes converts & quiescent foo0~ tp) sn active one: In 47% of eases $28n by MP.$14 PEDIATRICS AND CHILD HEALTH Tavera, trauma was a contributory factor and the onset of the signs and symptoms ‘were traced directly to the accident. Blood: borne dissemination is perhaps not the sole cause of spinal tuberculosis. In view of the anatomic relationship between the lymphaties of the neck, thorax and abdomen with the vertebral bodies, infection can extend by contiguity. Clinical Manifestations. Rigidity of the spine due to muscular spasm is an out- standing sign. In cervical spine involvement, the neck is stiff and the child is unable to turn his head or to move it from side to side or up and down without the trunk following the movement of the head. The child tends to cup his hand under his chin so as to support his head. Accidental jarring elicits a sharp cry of pain. The child with involvement of the thoracic vertebrae avoids stooping, walks stiffly, slowly and limps. On physical examination there is either fullness over the ‘spine or the presence of a knuckle which on tapping elicits pain. In involvement of the lumber vertebrae, the typical stance is with the feet far apart, Symptoms of compression myelitis are more common when the cervical and upper thoracic vertebrae are inyolved because the spinal canal is narrowed at this level. Exaggeration of the reflexes of the ankles and knees precedes the paraplegia. Sensory, motor and bladder disturbances may be found. Another outstanding symptoms is the so called “night cries”, which at first are dismissed as due to nightmares. These sharp cries of pain tend to come with alarming frequency, and are due to the relaxation of the protective muscular spasm during sleep. A paravertebral abscess can be detected tadiographically before. it appears. super- ficially and becomes palpable. Rupture of a retropharyngeal abscess due to cervical vertebral involvement can cause death from ‘asphyxia due to flooding of the airways. by ‘tS caseous contents, Occasionally, the ‘abscess points in the neck or supraclavicular ee ene in the region ‘groin but does there is referred pain in one Jeg and a limp. Roentgenography. Notehi anterior edges of the vertebral hodieg agit seen, as well as the compression of the anterior portions of the vertebral boda ang disappearance of the intervertebral sp Paravertebral abscesses appear as spindlg: shaped densities lateral to the spine, Prognosis. This is favorable when the case is seen early. Healing by ankylosiy results in permanent stiffness of the sping, Transverse myelitis demands immediate surgical, intervention in order to. release pressure on the cord before paraplegia becomes permanent. Advanced cases with severe angular kyphosis may not be cor rected by surgery. Severe. kyphosis. with crowding of the ribs causes secondary respiratory insufficiency and ultimately cor pulmonale, TUBERCULOSIS OF THE SKULL, OTHER BONES AND JOINTS Tuberculosis of the skull is extremely rare. It usually presents as multiple, soft, painless swellings and roentgenogram of the skull reveals punched-out areas of bone destruction; the same process may be found in other bones (osteitis tuberculosa multiplex cystica, Jungling’s disease). Next to. the spine, the hip, knee and ankle joints appear to be susceptible to the implantation. and proliferation of tubercle bacilli. Trauma contributes by activating a quiescent focus. Functional use and age influence the predilection of the disease for those joints. The pathology in skeletal tuber- culosis is characterized by degeneration, destruction and repair. ‘Tuberculosis can involve any bone in the skeletal system. Involvement of the costal cartilages or ribs appears to be associated with an underlying pleural pathology. and @ cold abscess may form, which may be con fused with empyema necessitatis, It can also be mistaken for a caseous lymphadenitis if it presents itself in the axilla, Osteo changes. in the affected ribs. are radiography.| __asis of the joints, pain is a prominent symp. ; tomsince joints are directly affected by mo. tion. It is generaily localized. rather than referred to other areas, except in tuberculosis ofthe hip where the pain may be referred to theyknee. Stiffness is an early symptom Because the child restricts motion of the affected joints. When the child moves during + sleep, he screams from pain. It tends’ to be felt more in the moming due to the decrease inthe synovial fluid andthe child seems to limp less. There may be some degree of swel ling visible over the superficial joints and it becomes more prominent as the muscle atrophy. Tuberculosis of the elbow, shoulder ‘and wrist joints is rare. \cro-iliac involvement. isthe rarest and the most fatal because it is seldom diagnosed early Roenigenography. Roentgenographic thanges may not be evident in the early Stages: The hip joint may show an erosion inthe head of the femur or in the margin of the:acetabulum. In the knee, changes are seen in the epiphysis of the tibia or femur and only occasionally in the patella. Signs Of synovitis may also be seen. OTHER FORMS OF TUBERCULOSIS ‘TUBERCULOSIS OF THE MOUTH AND UPPER RESPIRATORY TRACT Tuberculosis of the Tonsils and Ade- noids. It should be suspected in the presence of phylctenules of the conjunctiva, slight or moderate painless enlargement of the cervical lymph glands, and painless en- Jargement of the tonsils characteristically devoid of exudates. Chronic Otitis and Mastoiditis. Tuber gulosis of the middle ear appears to be com- mon ‘in Filipino children and may be sus- pected in the presence of chronic otitis media Tot accompanied by fever or pain, and asso ‘ciated with painless enlargement of the Preaurical and postauricular lymph glands. the aural discharge is serous, but is purulent since secondary in- generally coexists. Deafness and 1, TUBEROULOSIS 515 is the nasopharynx from where: the: bacilli are propelled along the eustachian tube, The mastoid cells become infected from the tympanic cavity, or occasionally through the blood stream. The immediate danger from tubereulous mastoiditis is the extension of the infection to the meninges. A striking feature of tuberculous mastoiditis is the lack of pain, Diagnosis is confirmed by isolating tubercle bacilli from the aural dua by biopsy of the granulation tissue, The presence of other active foci aids in the diag- nosis. Chemotherapy should be instituted early in order to prevent permanent loss of hearing, The role played by secondary bacte- rial infection should not be overlooked and cultures and sensitivity studies should be done. Laryngeal Tuberculosis. Infection, of the larynx in both children and adults is caused by contact. with. tubercle bacilli in the sputum. This is occasionally found in children with progressive pulmonary tuber- culosis and in those with chronie pulmonary tuberculosis. The symptoms are hoarseness and pain on swallowing or coughing. RENAL TUBERCULOSIS Children with miliary tuberculosis*or progressive primary tuberculosis may pyuria and albuminuria but tuberele bacilli can be demonstrated by smear and culture in only a few cases. According to Medlar, bacilli cannot pass through an intact neph= ron; hence, bacilluria always indicates a focus of active disease. During the early phase of primary ‘tuber- culosis, the kidneys are seeded by bacilli transported by the blood stream. In many children, these lesions regress spontane- ously; in a few progression occurs soon: after seeding. In others, the lesions become quiescent, progressing years later ind resulting in destructive renal tubereulosist Renal involvement: should be ‘suspected in patients with destructive pulmonary: tuber culosis who present persistent pyuria from: which no pyogenic organisms ¢anobe’ = tured. In addition, there is hematuria. albuminuria, Repeated cultares, a8, wel saber 4a full urologic investigation is516 PEDIATRICS AND CHILD HEALTH those with persistent pyuria. Renal tuberculosis responds well to chemotherapy. Treatment should be conti: nued indefinitely for those with extensive renal disease in order to prevent a relapse. Repeated: urinalysis every 6 months and carried into adult life is advisable. OCULAR TUBERCULOSIS ‘The common forms of ocular lesions seen are conjunctivitis and phlyctenular kerato conjunctivitis. The latter lesion results from the atopic reaction of a hypersensitive con- jumetiva or cornea to tuberculin. Phlycte- nules are generally associated with tuber. eulous disease of the tonsils and adenoids and occassionally of the middle ear. It is the author's belief that the mode of infection is ot through the blood stream but a direct one. Tubercle bacilli are transmitted from the lower respiratory tract to the nasal passages and to the Iscrimal glands. The bacilli may also be implanted on the ocular surface from superficial exuding lesions such 8 Serofuloderma, otitis media and ruptured old abscess secondary to tuberculous osteo- myelitis. Ocular disease can result in partial or total loss of vision. Tuberculosis of the Incrimal gland causes scarring of the eyelid and-if extensive, it leads to eversion or in- version of the eyelid. Subsequent involve ment of the inner layers of the eye may oveur. Slit lamp examination will: reveal keratie precipitates appearing as discrete or conglomerate granules dotting the iris, In miliary tuberculosis, choroidal tuber. cles may be seen on fundoscopy long before Xcrays can reveal tubercles in the pulmonary fields, CUTANEOUS TUBERCULOSIS Primary Tuberculosis of the Skin. Invrare instances, the skin is the portal of entry for: tubercle bacilli. A. wound. which does not heal readily and is accompanied by atinless-swelling of the regional lymph nodes Should arouse suspicion and a tuberculin test should be don + Serofuloderma, This is a form of cuta- Meous tuberculosis usually associated with ‘caseous lymphadenitis and osteomyelitis and Hnvolvement.of the overlying skin. The lesions are usually located in the neck, skin ulcers appoar moist, dirty and are ge vered with exuberant ugly scars usually result. Rifampicin-INH combination appears ty effective treatment, Healing jg more rapid and scar formation is seanty. Lupus Vulgaris. Tubercle bacilli are not easy to demonstrate in lesions, unlike in serofuloderma. Lupus is usually found on the face, frequently on the cheeks but any part of the body may be affected. The rex Ponse to treatment is slow: The addition of steroids to the specific antimicrobials is said to hasten the clearing of the skin lesions. Verrucosa Cutis. These are wartlike lesions which occur as a result of local eontaet with tubercle bacilli. They appear to be com mon on the dd dorsum of the hands. Papulonecrotic Tuberculids. These are the early cutaneous manifestations of blood stream dissemination. They are of diagnostic value because they indicate recent hematogenous spread. Tuberculids resemble the small lesions of chickenpox but are more indurated. PROPHYLAXIS BCG Vaccination. This is the simplest, safest, most economical and ‘most effective measure for the prevention of tuberculosis in countries where there is a high prevalence of the disease. In the last 30. years, some 400 million children all over the world have been vaccinated with BCG, It has been adopted as a national policy in many countries including the Philippines. BOG vaccination may reduce the lifelong risk of endogenous reactivation associated with foci ‘acquired from infection during childhood, In view of its potential for tubereulosis control, BCG vaccination has been widely used in developing countries and is included in the Expanded Programme on Immunization. ‘The BCG vaccine is a preparation of live attenuated bovine tubercle bacilli named aft ter Calmette and Guerin. The vaceine is ideally administered during the early neo natal period and repeated before entering primary school. BCG may be given orally subeutaneously, by multiple skin puncture or by intradermal injection, (the last method granulation. tismuge being, given: over th limina auired practi sures ¢ culin { dence when } simult Jong a Th produe Calme instea be cau mediat ‘minim “a which ¢ a smal Primary prophy Secondarybeing preferred.) The freeze dried yaccine ig given at a dose of 0.05-0.1 mL intradermally over the deltoid muscle, The practice of pre liminary tuberculin testing is no longer re. quired and direct vaccination is standard practice. Use of the freeze-dried vaccine en- sures effectiveness so that a post-BCG tuber culin test becomes unnecessary. The inci. dence of local complications is negligible when properly administered. It can be given simultaneously with other immunizations as Jong as separate sites are utilized. The rationale of BCG vaccination is to produce a primary infection caused by the Calmette Guerin bacillus which is harmless, instead of the primary infection which may be caused by M. tuberculosis, Host cell mediated immunity is thus activated with minimal chance of progressive disease. A wheal results after the vaccination which disappears after about half hour. Then a small tender swelling about 10 mm: 15. TUBERCULOSIS 517 appears after about 2 we After another 2 to 3 weeks the swelling becomes a small abscess which may then ulcerate As to the effectiveness of BCG yaecina- tion Goldits et al evaluated in their studies that in newborns and infants BCG vaccina- tion significantly reduces the risk of TB by over 50%, Udani had similar. favorable con- clusions in the protective value of BCG vacei- nation. Locally, Galicia of UP-PGH showed 15% reduction in risk from TB meningitis if BCG is given in the first year of li BCG revaccination is not uniformly ac- cepted. Thus WHO states that. available evidence does not support repeated vaeci- nation so that the practice is not indicated. A Hungarian study emphasizes one BCG vaccination is not sufficient so that a booster dose is recommended but there was.no comparative control in their study. Primary Chemoprophylaxis..See Table 15.1 on TB Chemoprophylaxis. IDELINES FOR TB CHEMOPROPHYLAXIS* iSicgas Pers Wiph Wek otliastion Dania ct eet aee imary chemo- _ Newborn of an infected mother ‘3 months initially; after $ pees sa Ee carotene ment gemsiieee eee one eS oe ae A enti m H for 6 months more; if abnormal chest ae ae HIV fnfection/perabine witli Hek 12 months ee ae uy Tro yeti alse liN aon pci pr wiaishasarisasees Coe eteneodse oe 1-2 months ‘8. Measles/pertussis, te Conditions/drugs that induce ae een chronic dialysis, leukemia. ‘Brom: National Consensus on Childhood Tuberculosis. {or the duration ofthe immunosuppression$18 PEDIATRICS AND CHILD HEALTH Secondary Chemoprophylaxis. See Table on TB Chemoprophylaxis. Public Health Measures. Tuberculosis has been controlled in health-motivated nations which have succeeded in improving socio-economic conditions and in enforcing health program aimed at intensive health education, case-finding, treatment of con tagious cases and prevention through wide application of BCG. A national TB control program includes three approaches, namely: 1. BOG vaccina- tion of children; 2. detection of infectious cases by sputum microscopy; 3. ambulatory chemotherapy of bacteriologically confirmed cases. These methods have been proven to be effective in breaking the chain of con- tinuous spreading of tuberéulosis in the community, and at the same time establish priorities in the treatment of TB case, the target being the protection of the younger generation and the treatment of the main infectious sources so as to render them non. infectious as rapidly as possible. ‘TB CHEMOPROPHYLAXIS (See Fig. 16.8 and Table 16.1) Isoniazid (INH). The larger dose is indicated in children with more serious forms of tuberculosis and.in those.who do not respond. promptly Monoprophylaxis with INH alone is re ‘commended by those who advocate, primary chemoprophylaxis. For curative purposes, INH should be combined with one or more drugs not only to maximize results but to delay drug re= Even in the presence:of resistance INH is continued in combination with other drugs to which there is no resistance so that some of the beneficial be availed of. Rifampin (RMP). This is the most effec tive anti-TB drug discovered since the disco very of INH. It has a powerful bactericidal action, Maximum results are obtained in ig Tegimens containing RMP on a dail basis for six months. vee ‘The higher dosage is recommended for the Bee serous form including TB meningitis. The drug is. given in @ single daily dose on an empty stomach, a ‘Anotable effect of RMP is the rapid rag. ponse of lymphadenitis as well as the seang amount of searification. Histological ex minations showed that RMP induces teso. lution of the disseminated foci up to complete disappearance of the lesions. Ethambutol (EMB). Adversé effeets in children have not been observed, In patients with decreased renal function the dosage should be adjusted since the main path of excretion of this drug is through the kidneys, Streptomycin (SM). Daily injections should always be given at the onset of therapy. The intermittent method is not as effective as when SM is administered daily. Only after improvement has occurred, bacteriological conversion attained and the disease brought under control can the daily injections of SM be reduced to 2 or 3 times a week until 40-60 gms (at most 100 gms) of SM have been consumed. In serious complications of tuberculosis such as meningitis or miliary tuberculosis, V2 gm of SM every 12 hours is advised, regardless of the weight of the child, until such time that survival seems assured. ‘Then the dose in relation to body weight and given only once a day SM should not be given as the sole agent because bacterial resistance develops more rapidly Morphazinamide Hydrocholoride (MZA). MZA is pyrazinamide derivative (PZA). Ibis a very effective anti-TB drug es- pecially in caseous forms of TB. Excellent results are obtained in combinations con- taining this pyrazinamide derivative. It isa very effective anti-TB drug especially in easeous forms of TB. Excellent results are obtained in combinations containing this pyrazinamide derivative. Para-aminosalicylic Acid (PAS). The usual daily dose for PAS is 200 to 300 mg/ kg of body weight divided into 3 doses. PAS is the weakest among the anti-TB drugs. ‘Those that advocate its use argue that the Presence of PAS delays the emergence of resistant strains of tubercle bacilli. Gastri¢ irritation to PAS and refusal of children t0 swallow many tablets every day for many ‘months makes the use of PAS undesirable: Steroids. These are intended only 85 the We ba ore dr be of to led ex‘ah adjunct to chemotherapy in order to curb the inflammatory processes and to neutra- ize the toxic by-products of the tubsrcle bacilli: The use of steroids is definitely eon- traindicated unless combined with anti-TB drugs. Tuberculous meningitis is probably the Dest indication for the use of steroids because fof its detoxifying effect, as well as its ability to modity inflammatory exudate which may Jead to a spinal block. Steroids are also used extensively in tuberculous endobronchitis in ‘order to prevent strictures. A telectasis due to permanent bronchostenosis is unaffected iby the addition of steroids. The effect of ste- roids is neglible in tuberculous adenopathies Rapid resolution of effusion in pleurisy is attributed to steroid. Treatment-failures. These result from. the use of substandard dosages, irregularity in taking the drugs, inadequate drug regi- mens, the premature discontinuation of therapy, and the presence of drug resistant infections at the start of treatment. Chemotherapy in children with tubercu- losis is more complex than in adults, so that regimens for adults are not applicable: Child~ ren need a precise dosage of the drug based on weight rather than the standardized drug combination and dosage. With major ad vances that have recently been attained in drugs against tuberculosis, there are now a number of short-course regimens of 6-9 months which have been proven to be highly effective, with low toxicity and are well tole- rated. There are different courses Such as daily regimens, or intermittent courses after fan initial intensive daily phase and somé fare intermittent throughout. These potent Tegimens are based on initial intensive phase of isoniazid, rifampicin and pyrazinamide ‘bupplemented by a fourth drug, streptomycin ethambutol, and isoniazid plus rifampicin the continuation phase. ‘The use of short-course chemotherapy has Been recommended in the continuation phase. | The use of short-course chemotherapy recommended in a number of tech- advanced countries and in some ‘countries national programs al- follows short courses. The major drug Satake aot hots i i t “Base? a'se G5 SRREREw 15 TUBERCULOSIS 519 combination of a shart:eo \erapy b short-course chemoth consists of any three or four of the following: ANNOTATIONS For FIG PREVENTIVE THERAPY OF CHILDHOOD TUBERCULOSIS (A) TB Exposure (Class 1): Includes persons with significant contact with ado- lescent/adult source case but who are asymp- tomatic, with negative Mantoux Test and normal radiologic findings. ) Children particularly those under 5 years old, can develop severe TB in less than 3 months (6-8 weeks in meningitis and dis- seminated disease) because of the short incubation period of pulmonary, CNS and disseminated diseases. Hence, infants and young children in the exposure stage should receive preventive therapy. In older children preventive therapy in TB exposure is more controversial since the disease is slower in progression, However some experts recom- mend early treatment in the children to prevent establishment of infection after deposition of infected droplet nuclei in the alveoli, especially in the présence of risk factors like severe undernutrition and other immuno-compromised states. (©) Mantoux Test Positive = 3 5 mm induration in those without BCG sear; > 10 mm induration in those with BCG scar in the absence of any other findings suggestive of TB since BCG vaccination can cause in- creased reactivity to a subsequent tubereulin test. Virtually all children vaccinated at birth have non-reactive Mantoux test by 5:years of age. (D) For persons'exposed to infectious TB but not yet infected isoniazid (H) is given to prevent establishment of infection (primary, chemoprophylaxis). In this case H is protec: tive only while the person is receiving the drug. fz) Assuming that infector has been given adequate multiple drug therapy. 9 (E) TB infection: includes those positive: with Mantoux test but without signs and symptoms and radiologic evidences sugzes- tive of TB. Virtually all infected should be treated to prevent de TB disease in the near or